Diseases caused by brain energy supply defects can be innate (fibromyalgia secondary to
familial mitochondrial disorders) or acquired (tardive dyskinesia or weight gain associated
with prolonged antipsychotic use). Patients with these possible mitochondrial disorders will
provide a baseline resting heart rate sample, ingest low-dose metformin (500 mg), and then
provide an additional sample 2 hours later.
Doctors need to develop tests which inexpensively and reliably evaluates brain metabolism.
Current diagnostic tests sample other tissues which often run on different fuels (fats),
utilize unproven and often insensitive brain imaging scanners, or sequence thousands to
millions of base-pairs of DNA. All of these tests are expensive. None of these tests
accurately or completely capture the interactions between the 1000s of proteins involved in
The investigators suspect that mathematical analysis of the resting heart rate may provide
some insight into brain metabolism. The brain controls heart rate in response to changes in
blood pressure and blood gases like carbon dioxide and oxygen. Tight control of heart rate
is necessary to make sure that the brain has the right mix of fuel and air. Because the
brain can't respond instantly to changes in its fuel supply, this system acting as a
biological carburetor has a natural oscillatory rhythm that can be monitored just like
frequencies on the radio.
The investigators propose to amplify these rhythms by modestly metabolically stressing the
brain with metformin, a inhibitor of complex 1 in the mitochondria.
EITHER chronic neurogenic pain meeting ACR criteria for fibromyalgia or previous/current
exposure to antipsychotic medications
- recent infection,
- renal failure,
- pre-existing cardiac disease,
- inability to participate in informed consent,
- lack of transport to return home from study site,
- severe fasting intolerance or hypoglycemia,
- history of stroke-alike episode,
- uncontrolled migraine or cyclic vomiting,
- diabetes on insulin or sulfonylurea,
- non-English speaker,
- medications with strong effects on baseline heart rate variability